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Biomedical subjects

C Mathews

Publications and source records attributed to C Mathews.

13 recordsLinked to original sources
PubMed1992

Effects of acute and chronic blockade of neutral endopeptidase with Sch 34826 on NaCl-sensitive hypertension in spontaneously hypertensive rats.

We have previously demonstrated that dietary NaCl supplementation is associated with increased circulating atrial natriuretic peptide (ANP) levels in Wistar-Kyoto (WKY) rats but not in spontaneously hypertensive rats (SHR), and that replacement with exogenous ANP prevents NaCl-sensitive hypertension in NaCl-sensitive SHR (SHR-S). The current study tested the hypothesis that chronic administration of the neutral endopeptidase (NEP) inhibitor Sch 34826 prevents NaCl sensitive hypertension in SHR-S by increasing endogenous ANP. Male SHR-S received Sch 34826 (90 mg/kg/day) or vehicle by gavage for 4 weeks beginning immediately before the initiation of 1% or 8% NaCl diets at age 7 weeks. Sch 34826 prevented the increase in arterial pressure in response to 8% NaCl in SHR-S, but had no effect on blood pressure in 1% NaCl fed SHR-S; plasma ANP levels were increased by 63 and 68% in the 1% and 8% NaCl groups, respectively, in response to Sch 34826. To examine the mechanism(s) of the antihypertensive effect of Sch 34826 in NaCl-supplemented SHR-S, a single dose (90 mg/kg) of Sch 34826 or vehicle was administered by gavage to SHR-S that had consumed 1% or 8% NaCl diets for 3 weeks. Sch 34826 abolished the NaCl-induced increase in blood pressure 3 h after treatment in 8% NaCl fed SHR-S, but had no effect in SHR-S fed the 1% NaCl diet. This effect was associated with increased urine volume and urinary sodium, ANP, and cyclic GMP in 8% NaCl fed SHR-S.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Environmental determinants of acute respiratory symptoms and diarrhoea in young coloured children living in urban and peri-urban areas of South Africa.

The impact of environmental risk factors associated with housing was examined in relation to diarrhoeal disease and acute respiratory symptoms in South African coloured children. A multistage cluster sample representative of all coloured people living in the major urban and peri-urban areas of South Africa was used for the study. Interviews were conducted with respondents from 1,227 households. Overall, 8.5% children under 5 years were reported to have had diarrhoea, while 29% had experienced coughing and breathing problems in a 2-week recall period. Individual risk factors identified using the odds ratios (ORs) for diarrhoea included not having an inside tap or a flush toilet in the homes (both yielded an OR of 3.3), not owning a refuse receptacle (OR = 2.5), not being connected to an electricity supply (OR = 2.5), low household income (OR = 1.8), more than 2 people per room (OR = 2.0) and less than Standard 5 maternal education (OR = 1.6). Absence of an inside toilet, not having a refuse receptacle and overcrowding all remained as independent risk factors after logistic regression analyses. Multiple logistic regression analyses revealed that not having a refuse receptacle and the absence of electricity for heating purposes were independently associated with respiratory symptoms. The overall preventive potentials for respiratory symptoms were significantly less than those for diarrhoea. Improving physical access to essential environmental health services in urban areas and improvements in the educational status of women are urgently needed if childhood infections are to be prevented.

Black or African American↗
PubMed1991

Evaluation of a peri-urban community health worker project in the western Cape.

The South African Christian Leadership Assembly (SACLA) Health Project is a non-governmental organisation that runs a community health worker (CHW) programme in 4 peri-urban townships of Cape Town. A cross-sectional descriptive community survey was conducted in April 1990 to evaluate coverage and health education on oral rehydration solution (ORS) and to plan future preventive, promotive and development programmes. Research concepts and methods were made accessible to the CHWs through a training process designed to facilitate participation in every stage of the research. A multi-stage cluster sampling scheme was used, and the CHWs interviewed 822 residents. Coverage indicators showed that over 80% of all respondents had previously known about or consulted the CHW. The most common community problems related to water, filth and refuse, toilets, housing, unemployment and lack of community facilities. The most common health problems were generalised aches and pains, chest problems, skin problems, worms, and diarrhoea. An index developed to measure knowledge of ORS showed very few respondents had 'complete knowledge'. The community's expectations of the CHW included health education, attending to sanitation problems, providing a clean environment, organising community facilities, and helping with employment.

Community Health Services↗
PubMed1991

Expression of ras genes in rainbow trout liver.

Members of the ras gene family have been studied in a variety of species. Two ras genes expressed in the normal liver of rainbow trout, ras-1 and ras-2, as well as a portion of a genomic ras-1 allele, are described for the first time in this report. Over 500 bp of trout ras-1 and at least 300 bp of trout ras-2 genes expressed in normal liver have been sequenced; DNA homology to the human ras genes ranges from 76.8% to 87.1%. The base changes resulting from over 400 million years of evolutionary divergence between the species were primarily silent, with few changes in protein sequence. The partial DNA sequence of the genomic ras-1 allele has 86.8% homology to the first two exons of human c-Ha-ras, and its intron has several conserved sequences characteristic of vertebrate intron-exon junctions. However, the predicted amino acid sequence of trout ras-1 differs at only one of the first 172 amino acid residues from human c-Ki-ras with the alternate exon 4b. Since trout ras-1 differs at 17 and 18 residues from the human c-N-ras and c-Ha-ras proteins, respectively, over this region, we conclude that trout ras-1 is a c-Ki-ras gene. The highly conserved nature of this gene suggests that the ras p21 protein has identical functions in normal and neoplastic cells among higher and lower vertebrates.

Animals↗
PubMed1991

Analysis of ras gene mutations in rainbow trout liver tumors initiated by aflatoxin B1.

The suspect human hepatocarcinogen aflatoxin B1 (AFB1) is a well-known potent initiator of hepatic tumors in rainbow trout (Oncorhynchus mykiss). Both hepatocellular carcinomas and mixed hepatocellular/cholangiocellular carcinomas are induced by AFB1 in trout, with the mixed form predominating. We previously isolated two c-ras genes from trout liver cDNA, and in the present study we analyzed DNA from 14 AFB1-induced trout liver tumors for point mutations in exon 1 of both genes. Using the polymerase chain reaction (PCR) and oligonucleotide hybridization methods, a high proportion (10/14) of the AFB1-initiated tumor DNAs showed evidence of activating point mutations in the trout c-Ki-ras gene. Of the 10 mutant ras genotypes, seven were codon 12 GGA----GTA transversions, two were codon 13 GGT----GTT transversions, and one was codon 12 GGA----AGA transition. Nucleotide sequence analysis of cloned PCR products from four of these tumor DNAs provided definitive evidence for two codon 12 GGA----GTA mutations, one codon 12 GGA----AGA mutation, and one codon 13 GGT----GTT mutation, in complete agreement with the oligonucleotide hybridization results. No mutations were detected in exon 1 of a second trout ras gene also expressed in liver, nor in DNA from control livers. This is the first report of experimentally induced ras gene point mutations in a lower vertebrate fish model. The results indicate that the hepatocarcinogen AFB1 induces c-Ki-ras gene mutations in trout similar to those in rat liver tumors.

Adenoma, Bile Duct↗
PubMed1990

Knowledge, attitudes and beliefs about AIDS in township school students in Cape Town.

Students (N = 377) from four Cape Town township high schools were surveyed to obtain information on their knowledge of and attitudes towards the acquired immunodeficiency syndrome (AIDS), and on their sexual behaviour. The study was undertaken to provide information for planning an AIDS education intervention. Three-quarters of students reported that they had had sexual intercourse. Most students had heard of AIDS, and the majority of these knew that it was infectious. More than half of the students were confused or lacked knowledge about the modes of transmission. Two-thirds of the students believed AIDS could be prevented, but knowledge of prevention strategies was superficial. Of the sexually active students only 11.4% had ever used a condom, and of all students 39.6% stated that they would use a condom in the future. Two-thirds of the students were not aware that there is no cure for AIDS. Students did not acknowledge that AIDS could affect them directly, and attributed the problem to prostitutes and 'promiscuous' people in 36.4% of responses, and to 'white' people in 23.8% of responses. Students expressed intolerance, fear and rejection of people with AIDS, and only 6.4% would accept an affected person into their class. Almost all the students wanted AIDS education at school, and most of these requested that the school nurse facilitate this education. It is concluded that appropriate AIDS prevention education is urgently required for both high school and junior school students.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Urbanisation and health: methodological difficulties in undertaking epidemiological research in developing countries.

Rapid urbanisation has historically resulted in complex societal changes which have had both beneficial and adverse effects on the health of communities. Recently, it has been recognised that the urban poor in developing countries are at greatest risk for several adverse health effects. The epidemiologist has a key role to play in planning to meet current and future health needs of urban communities. Epidemiological research needs to focus on understanding the relationship between the changes that occur with urbanisation and their impact on health, in order to identify those at greatest risk, to identify the important risk factors that are amenable to intervention, and to evaluate the effectiveness of interventions aimed at improving the health of urban communities. This paper addresses several methodological difficulties in conducting epidemiological research on urbanisation and health in developing countries, with particular reference to Southern Africa. These relate to the definition of urban areas and residence thereof, the comparability across areas of exposure and outcome information, the identification of intra-urban variability, selection bias in cross-sectional studies, associating outcomes with specific urban exposures in analytic studies, and determining appropriate interventions and means of evaluation. Ways of overcoming these difficulties are suggested. Epidemiologists need to address these issues in order to make a valuable contribution to the improvement of health in urban communities.

Bias↗
PubMed1989

The relation between hospital experience and in-hospital mortality for patients with AIDS-related PCP.

There is marked debate by physicians and policymakers regarding the creation of regionalized acquired immunodeficiency syndrome (AIDS) centers. A central issue is whether outcomes of care, particularly mortality, differ as a function of hospital experience with patients with AIDS. We evaluated the experience of 257 patients with AIDS and Pneumocystis carinii pneumonia treated at 15 California hospitals between October 1986 and October 1987. An overall 15.2% in-hospital mortality rate was observed. However, a markedly lower in-hospital mortality rate was observed in the group of patients treated at hospitals that had a high level of experience with patients with AIDS (greater than or equal to 30 human immunodeficiency virus-related discharges per 10,000 hospital discharges) relative to the group treated at hospitals with less experience (less than 30 human immunodeficiency virus-related discharges per 10,000 hospital discharges): 12% vs 33%. Other factors significantly associated with in-hospital mortality included intensive care unit use, admission from an emergency department or through an interhospital transfer, and a history of hospitalizations. A logistic regression model indicated that, after controlling for severity indicators, AIDS experience remained significantly related to mortality. Our findings suggest that policymakers should consider three options: creating regional AIDS centers, implementing policies that promote a rapid but carefully monitored increase in experience of low-volume hospitals with human immunodeficiency virus-infected individuals, or providing highly focused educational efforts at low-AIDS-experience facilities. Without such policy initiatives, differences in mortality rates like those we have found might persist as cases of AIDS begin to occur in every area of the country.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Vaccinia virus-encoded ribonucleotide reductase: sequence conservation of the gene for the small subunit and its amplification in hydroxyurea-resistant mutants.

The vaccinia virus gene that encodes the small subunit of ribonucleotide reductase was localized to the HindIII F fragment by using degenerate oligonucleotide probes. DNA sequencing revealed a leftward-reading open reading frame that predicted a protein of 37 kilodaltons whose amino acid sequence was much more homologous to the mouse and clam M2 sequences (approximately 80%) than to the corresponding herpesvirus (approximately 27%) or procaryotic (approximately 19%) gene products. Vaccinia virus mutants selected for the ability to grow in high concentrations of a specific inhibitor of ribonucleotide reductase, hydroxyurea, amplified the M2 gene and harbored tandem arrays (2 to 15 copies) of the gene within the HindIII F region. RNA isolated at early times after infection with wild-type virus and probed with an internal fragment of the M2 gene indicated one major (1.2 kilobases) and two minor (4.0 and 2.1 kilobases) transcripts. S1 nuclease analysis and primer extension experiments identified an RNA start site 12 nucleotides upstream of the putative initiation ATG codon.

Amino Acid Sequence↗
PubMed1976

A simple, rapid method for prenatal detection of defects in propionate metabolism.

Incorporation of radiolabel from propionate-1(-14)C into protein (TCA insoluble material) in fibroblasts or amniotic fluid cells, provides a rapid, simple means of detecting fetuses with inborn errors of propionate metabolism using small numbers of cells. Controls were easily differentiated from mutant lines over differing media pH conditions. This method was successfully used to diagnose correctly a normal fetus at risk for methylmalonic acidemia. This method can be used as an adjunct in diagnosis, but cannot replace direct enzyme analysis.

Amniotic Fluid↗
PubMed1975

Studies of methylmalonyl coenzyme A carbonylmutase activity in methylmalonic acidemia. I. Correlation of clinical, hepatic, and fibroblast data.

Methylmalonyl-CoA carbonylmutase (mutase) activity was measured in fibroblast extracts from 15 patients with methylmalonic acidemia and in extracts of postmortem tissues from 6 of these children. Propionate oxidation and synthesis of 5-deoxyadenosylcobalamin (AdoCbl, the vitamin B12 coenzyme that is part of the mutase holoenzyme) were measured in intact fibroblasts. Mutase activity was low in the absence of added AdoCbl in fibroblast extracts from both control subjects and patients. When the assay included supplemental AdoCbl, mutase activity increased in the control subjects (to 24.0 pmol succinate/mg protein/min) and in extracts from eight of the patients (20.8 pmol/mg protein/min), but showed almost no change in extracts from the other seven patients (0.16 pmol/mg protein/min). We have defined the eight fibroblast lines that showed normal mutase activity in the presence of AdoCbl as "responsive lines" and the other seven lines as "nonresponsive." In the liver or kidney extracts of postmortem tissues, mutase activity responded to AdoCbl supplementation if fibroblast mutase activity from that patient had responded, and failed to respond if fibroblast activity failed to respond. Mean propionate oxidation in intact fibroblasts was much higher in control lines than in either responsive or nonresponsive lines (0.728 vs 0.097 vs 0.080 nmol CO2/10(6) cells/hr, respectively). AdoCbl synthesis was normal (0.27 pg AdoCbl/mg cells wet weight) in nonresponsive fibroblasts but was undetectable (less than 0.005 pg/mg cells) in the responsive lines. Thus, the deficiency of mutase activity in responsive fibroblast lines is due to the failure to synthesize significant amounts of AdoCbl, whereas the deficiency in nonresponsive lines is due to some other abnormality, presumably a defect in the mutase apoenzyme.

Animals↗